Thrombosis is the development of a ‘thrombus’(clot) consisting of platelets, fibrin, red cells and white cells in the arterial or venous circulation. If part of this thrombus in the venous circulation breaks off and enters the right heart, it may be lodged in the pulmonary arterial circulation, causing pulmonary embolism (PE). In the left-sided circulation, an embolus may result in peripheral arterial occlusion, either in the lower limbs or in the cerebral circulation (where it may cause thromboembolic stroke).

1. THROMBOSIS
-- Dr. S P Srinivas Nayak
Assistant Professor, SUCP
Hyderabad.

2. THROMBOSIS
• Thrombosis is the development of a ‘thrombus’(clot)
consisting of platelets, fibrin, red cells and white cells
in the arterial or venous circulation.
• If part of this thrombus in the venous circulation breaks
off and enters the right heart, it may be lodged in the
pulmonary arterial circulation, causing pulmonary
embolism (PE).
• In the left-sided circulation, an embolus may result in
peripheral arterial occlusion, either in the lower limbs
or in the cerebral circulation (where it may cause
thromboembolic stroke).

3. Since the pathophysiology of each of these
conditions differs, they will be discussed
separately under the headings
• ‘Venous thromboembolism’ (VTE) and
• ‘Arterial thromboembolism’.

5. Venous thromboembolism
• VTE is common, with an incidence of 2–5%. PE
is now the commonest cause of maternal
death, and deep vein thrombosis may result in
not only PE but also subsequent morbidity as
a result of the post-phlebitic limb.
• Thromboembolism appears to increase in
prevalence over the age of 50 years, and the
diagnosis is more often missed in this age
group.

6. Causes of VTE
• combination of stagnation of blood flow and
hypercoagulability.
• stagnation of blood flow may be related to bed
rest, surgery or reduced cardiac output, for
example in heart failure.
• Factors increasing the risk of hypercoagulability
include surgery, pregnancy, oestrogen
administration, malignancy, myocardial infarction
and several acquired or inherited disorders of
coagulation

8. SEVERAL GENETIC CAUSES
(Ref: Rosendaal and Reitsma, 2009).
1. Protein C & S deficiency
• Protein C deficiency patients are at increased risk not
only of VTE but also of warfarin skin necrosis Because it
is a vitamin K-dependent antithrombotic factor that
can be further suppressed by the administration of
warfarin
2. Factor V Leiden, a mutated form of human factor V
Due to this mutation, protein C, an anticoagulant
protein which normally inhibits the pro-clotting activity
of factor V, is not able to bind normally to factor V,
leading to a hypercoagulable state

9. 3. Antithrombin III deficiency
• Antithrombin III deficiency is a rare autosomal
dominantly inherited abnormality. The defect may not
result in clinical problems until pregnancy or until
patients enter their fourth decade., Nevertheless, it
has been estimated to be responsible for between 2%
and 5% of thromboembolism occurring before age 45.
4. Lupus anticoagulant antibody:
• This factor is found in 10% of patients with systemic
lupus erythematosus (SLE) where it is associated with a
threefold increase in thromboembolic risk

10. 5. Prothrombin 20210 mutation
• A mutation in part of the prothrombin gene
(prothrombin 20210A) results in increased
prothrombin concentrations and an increased risk of
venous thrombosis.
6. Oestrogens
• Oestrogens(OCP, HRT) increase the circulating
concentrations of clotting factors I, II, VII, VIII, IX and X
and reduce fibrinolytic activity. They also depress the
concentrations of antithrombin III.
7. Others: Surgery, Malignancy, age over 60, Dehydration,
pregnancy etc

13. Clinical manifestations
• In 90% of patients, deep vein thrombosis
occurs in the veins of the lower limbs and
pelvis. In up to half of cases, this may not
result in local symptoms or signs, and the
onset of PE may be the first evidence of the
presence of VTE.
• Tests performed may include: Venography,
ultrasound, MRI, Pulmonary arteriography,
spiral CT, etc.

14. TREATMENT
Goals:
1. Allow normal circulation BY clearing clot in PE’
2. Prevent damage of valves of the veins,
3. Prevent further PE, DVT attacks,
In acute massive PE, the initial priority is to correct the circulatory
defect that has caused the haemodynamic upset, and in these
circumstances, rapid removal of the obstruction using
thrombolytic drugs or surgical removal of the embolus may be
necessary.
• The treatment of VTE consists of the use of anticoagulants and, in
severe cases, thrombolytic drugs. Anticoagulant therapy involves
the use of immediate-acting agents (particularly heparin) and oral
anticoagulants, the commonest of which is warfarin. Not only do
these treat the acute event, but they also prevent recurrence.

15. HEPARINS
1. UFH(HEPARIN), LMWH(EDTA)
2. ADME
3. MOA (Acts by activating antithrombin III and inactivates
Xa, IIa, IXa, XIa, XIIa and XIIIa)
4. ADRS and CI
5. ADVANTAGES OF LMWH over UFH
• Loading dose
5000 iu over 5 min
• Infusion
Start at 1400 iu/h (e.g. 8400 iu in 100 mL of normal saline over
6 h).

16. COUMARINS
1. WARFARIN
2. MOA: (Acts by inhibiting synthesis and
carboxylation of vitamin K-dependent clotting
factors II, VII, IX and X)
3. ADME—
4. ADRs
5. INTERACTIONS:
i) inducers-CRAP GPS,
ii) inhibitors(SICK FACES.COM)
iii) Tetracyclines
iv) Aspirin and NSAIDs

21. Case study.1
A 25-year-old woman presents to the emergency department
complaining of acute onset of shortness of breath and pleuritic pain.
She had been in her usual state of health until 2 days prior when she
noted that her left leg was swollen and red. Her only medication
was oral contraceptives. Family history was significant for a history of
“blood clots” in multiple members of the maternal side of her family.
Physical examination demonstrates an anxious woman with stable vital
signs. The left lower extremity demonstrates erythema and edema and
is tender to touch. Oxygen saturation by fingertip pulse oximeter
while breathing room air is 87% (normal > 90%). Ultrasound reveals
a deep vein thrombosis in the left lower extremity; chest computed
tomography scan confirms the presence of pulmonary emboli.
Laboratory blood tests indicate elevated d-dimer levels.
What therapy is indicated acutely? What are the long-term therapy
options? How long should she be treated? Should this individual use
oral contraceptives?

23. ANSWER:
• This patient has pulmonary embolism secondary to a deep
venous thrombosis (DVT).
• Options for treating this patient include unfractionated
heparin or low-molecular weight heparin followed by
warfarin, with INR goal of 2–3.
• parenteral anticoagulation for 5–7 days followed by edoxaban
or rivaroxaban, apixaban, or dabigatran alone without
monitoring., the recommended duration of therapy would be
3–6 months depending on individual risk factors and
preferences.
• The patient should be counseled to use an alternative form of
contraception.

24. Case study.2
A 75-year-old patient receiving warfarin to
prevent deep vein thrombosis and previously
well controlled comes to the clinic with an INR
of 12, despite taking the same dose of drug.
There is no evidence of bleeding.
How will you treat him?

25. ANSWER:
• Since the patient's INR is >8 (even if there is
no bleeding), the national guidelines
recommend that warfarin be stopped.
• The patient should then be given
phytomenadione (vitamin K1) immidiately.
Check INR after 24hrs,
• If INR IS < 5 START warfarin
• If > 5 use one more dose of Vit.K